Position-based visual servoing of a 6-RSS parallel robot using adaptive sliding mode control.

The trajectory tracking control of parallel robots is challenging due to their complicated dynamics and kinematics. This paper proposes a position-based visual servoing (PBVS) approach for a 6-Revolute-Spherical-Spherical (6-RSS) parallel robot using adaptive sliding mode control in Cartesian space. A photogrammetry sensor C-Track 780 in the eye-to-hand configuration is adopted to measure the real-time pose of the robot end-effector, which can avoid the calculation of robot forward kinematics and provide more flexibility for controller design.

Utility of protein-protein binding surfaces composed of anti-parallel alpha-helices and beta-sheets selected by phage display.

Over the past 3 decades, a diverse collection of small protein domains have been used as scaffolds to generate general purpose protein-binding reagents using a variety of protein display and enrichment technologies. To expand the repertoire of scaffolds and protein surfaces that might serve this purpose, we have explored the utility of (i) a pair of anti-parallel alpha-helices in a small highly disulfide-bonded 4-helix bundle, the CC4 domain from reversion-inducing Cysteine-rich Protein with Kazal Motifs and (ii) a concave beta-sheet surface and two adjacent loops in the human FN3 domain, the scaffold for the widely used monobody platform. Using M13 phage display and next generation sequencing, we observe that, in both systems, libraries of ∼30 million variants contain binding proteins with affinities in the low μM range for baits corresponding to the extracellular domains of multiple mammalian proteins.

Experimental evidence of effective disinfectant to control the transmission of Micropterus salmoides rhabdovirus.

Micropterus salmoides rhabdovirus (MSRV) is a significant pathogen that causes high morbidity and mortality in largemouth bass, leading to enormous economic losses for largemouth bass aquaculture in China. The aim of this study was to investigate the efficacy of four disinfectants (potassium permanganate, glutaraldehyde, trichloroisocyanuric acid and povidone iodine) on MSRV, to control the infection and transmission of MSRV in largemouth bass aquaculture. The disinfectants were tested at different concentrations (5, 25, 50, 100 and 500 mg/L) prepared with distilled water for 30 min contact time, and the viral nucleic acid was quantified using qPCR and the infectivity was tested by challenge experiment.

A loop-mediated isothermal amplification-based microfluidic chip for triplex detection of shrimp pathogens.

Decapod iridescent virus 1 (DIV1), White spot syndrome virus (WSSV), and Enterocytozoon hepatopenaei (EHP) pose serious threats to the shrimp farming. To date, early detection remains an important way to control the occurrence and diffusion of these pathogens. Here, we developed for the first time, a loop-mediated isothermal amplification (LAMP)-based microfluidic chip detection system, which could detect DIV1, WSSV, and EHP simultaneously.

Bacteria reduce flagellin synthesis to evade microglia-astrocyte-driven immunity in the brain.

The immune response of brain cells to invading bacteria in vivo and the mechanism used by pathogenic bacteria to escape brain immune surveillance remain largely unknown. It is believed that microglia eliminate bacteria by phagocytosis based on in vitro data. Here we find that a small percentage of microglia in the brain engulf neonatal meningitis-causing Escherichia coli (NMEC), but more microglia are activated to produce tumor necrosis factor alpha (TNFα), which activates astrocytes to secrete complement component 3 (C3) involved in anti-bacterial activity.

Therapeutic development of group B Streptococcus meningitis by targeting a host cell signaling network involving EGFR.

Group B Streptococcus (GBS) remains the most common Gram-positive bacterium causing neonatal meningitis and GBS meningitis continues to be an important cause of mortality and morbidity. In this study, we showed that GBS penetration into the brain occurred initially in the meningeal and cortex capillaries, and exploits a defined host cell signaling network comprised of S1P , EGFR, and CysLT1. GBS exploitation of such network in penetration of the blood-brain barrier was demonstrated by targeting S1P , EGFR, and CysLT1 using pharmacological inhibition, gene knockout and knockdown cells, and gene knockout animals, as well as interrogation of the network (up- and downstream of each other).

Identification of a Compound That Inhibits the Growth of Gram-Negative Bacteria by Blocking BamA-BamD Interaction.

The demand for novel antibiotics is imperative for drug-resistant Gram-negative bacteria which causes diverse intractable infection disease in clinic. Here, a comprehensive screening was implemented to identify potential agents that disrupt the assembly of β-barrel outer-membrane proteins (OMPs) in the outer membrane (OM) of Gram-negative bacteria. The assembly of OMPs requires ubiquitous β-barrel assembly machinery (BAM).

Targeting E. coli invasion of the blood-brain barrier for investigating the pathogenesis and therapeutic development of E. coli meningitis.

Escherichia coli is the most common Gram-negative bacillary organism causing neonatal meningitis. Escherichia coli meningitis remains an important cause of mortality and morbidity, but the pathogenesis of E. coli penetration of the blood-brain barrier remains incompletely understood.

IMB-T130 targets 3-dehydroquinate synthase and inhibits Mycobacterium tuberculosis.

The anti-tuberculosis (TB) agent IMB-T130 was speculated to be a multi-target compound. In this research, we found that IMB-T130 inhibits the catalytic activity of Mycobacterium tuberculosis 3-dehydroquinate synthase (MtDHQS), the enzyme in the second step of the shikimate pathway. IMB-T130 was identified as a selective inhibitor of MtDHQS with an IC value of 0.

Identification of anti-Gram-negative bacteria agents targeting the interaction between ribosomal proteins L12 and L10.

Gram-negative bacteria have become the main pathogens and cause serious clinical problems with increased morbidity and mortality. However, the slow discovery of new antimicrobial agents is unable to meet the need for the treatment of bacterial infections caused by drug-resistant strains. The interaction of L12 and L10 is essential for ribosomal function and protein synthesis.

SIRT1 activator E1231 protects from experimental atherosclerosis and lowers plasma cholesterol and triglycerides by enhancing ABCA1 expression.

Background And Aims: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent protein deacetylase. Recent studies have demonstrated that enhancing SIRT1 expression or activity may modulate cholesterol and lipid metabolism. However, pharmacological and molecular regulators for SIRT1 are scarce.

Identification of TB-E12 as a novel FtsZ inhibitor with anti-tuberculosis activity.

The global pandemic of multidrug-resistant (MDR) Mycobacterium tuberculosis (TB) drives for more effective anti-TB drugs with new drug target. Filamentous temperature sensitive protein Z (FtsZ), a GTP dependent prokaryotic cell division protein, forms a dynamic Z-ring in the center of the cell. Differences between bacterial FtsZ and eukaryotic tubulin make FtsZ a highly attractive drug target.

A novel SIRT1 activator E6155 improves insulin sensitivity in type 2 diabetic KKA mice.

Sirtuin 1 (SIRT1) is an NAD-dependent protein deacetylase that plays a critical role in controlling energy metabolism, stress response and aging. Hence, enhancing SIRT1 activity could be a potential therapeutic strategy to treat metabolic diseases such as diabetes. However, pharmacological activators for SIRT1 are scarce to date.

Identification of a Novel Liver X Receptor Agonist that Regulates the Expression of Key Cholesterol Homeostasis Genes with Distinct Pharmacological Characteristics.

Activation of liver X receptor (LXR) is associated with cholesterol metabolism and anti-inflammatory processes, which makes it beneficial to antiatherosclerosis therapy. Nevertheless, existing agonists that target LXR, for example TO901317, are related to unwanted side effects. In the present study, using a screening method we identified IMB-808, which displayed potent dual LXR/ agonistic activity.

Discovery of the disubstituted oxazole analogues as a novel class anti-tuberculotic agents against MDR- and XDR-MTB.

A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed and synthesized. The newly synthesized compounds 1a-y were evaluated for their in vitro anti-TB activity versus replicating, multi- and extensive drug resistant Mtb strains.

Identification of an anti-TB compound targeting the tyrosyl-tRNA synthetase.

Objectives: Drug-resistant Mycobacterium tuberculosis poses a great threat to human health. Tyrosyl-tRNA synthetase (TyrRS) is one of the aminoacyl tRNA synthetases that catalyse the attachment of amino acids to their cognate tRNAs and are essential for protein synthesis. There are several distinctive differences between bacterial and human TyrRS and therefore it could be a potential target for developing antimicrobial agents.

Identification of a novel selective agonist of PPARγ with no promotion of adipogenesis and less inhibition of osteoblastogenesis.

Nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) plays an important role in the regulation of glucose homeostasis and lipid metabolism. However, current PPARγ-targeting drugs such as thiazolidinediones (TZDs) are associated with undesirable side effects. We identified a small molecular compound, F12016, as a selective PPARγ agonist by virtual screening, which showed moderate PPARγ agonistic activity and binding ability for PPARγ.

Identification of anti-tuberculosis agents that target the cell-division protein FtsZ.

Antibiotic resistance to Mycobacterium tuberculosis is a growing problem. Therefore, development of new anti-tuberculosis antibiotics is urgent for the control of tuberculosis (TB) infections. FtsZ, the homolog of eukaryotic tubulin, is a GTPase that assembles into cytokinetic Z rings essential for cell division in prokaryotic cells.

Rutaecarpine suppresses atherosclerosis in ApoE-/- mice through upregulating ABCA1 and SR-BI within RCT.

ABCA1 and scavenger receptor class B type I (SR-BI)/CD36 and lysosomal integral membrane protein II analogous 1 (CLA-1) are the key transporter and receptor in reverse cholesterol transport (RCT). Increasing the expression level of ABCA1 and SR-BI/CLA-1 is antiatherogenic. The aim of the study was to find novel antiatherosclerotic agents upregulating expression of ABCA1 and SR-BI/CLA-1 from natural compounds.

The antituberculosis antibiotic capreomycin inhibits protein synthesis by disrupting interaction between ribosomal proteins L12 and L10.

Capreomycin is a second-line drug for multiple-drug-resistant tuberculosis (TB). However, with increased use in clinics, the therapeutic efficiency of capreomycin is decreasing. To better understand TB resistance to capreomycin, we have done research to identify the molecular target of capreomycin.

Genetic organization of ascB-dapE internalin cluster serves as a potential marker for Listeria monocytogenes sublineages IIA, IIB, and IIC.

Listeria monocytogenes is an important foodborne pathogen that comprises four genetic lineages: I, II, III, and IV. Of these, lineage II is frequently recovered from foods and environments and responsible for the increasing incidence of human listeriosis. In this study, the phylogenetic structure of lineage II was determined through sequencing analysis of the ascB-dapE internalin cluster.

Genomic presence of gadD1 glutamate decarboxylase correlates with the organization of ascB-dapE internalin cluster in Listeria monocytogenes.

The ability to survive and proliferate in acidic environments is a prerequisite for the infection of Listeria monocytogenes. The glutamate decarboxylase (GAD) system is responsible for acid resistance, and three GAD homologs have been identified in L. monocytogenes: gadD1, gadD2, and gadD3.